Toxicity profile and Patient-Reported outcomes following salvage Stereotactic Ablative Radiation Therapy to the prostate Bed: The POPART multicentric prospective study.

Background: While SBRT to the prostate has become a valuable option as a radical treatment, limited data support its use in the postoperative setting. Here, we report the updated results of the multicentric Post-Prostatectomy Ablative Radiation Therapy (POPART) trial, investigating possible predictors of toxicities and patient-reported outcomes. Methods: Patients with PSA levels between 0.1-2.0 ng/mL after radical prostatectomy received Linac-based SBRT to the prostate bed in five fractions every other day for a total dose of 32.5 Gy (EQD21.5 = 74.3 Gy). Late toxicity was assessed using CTCAE v.5 scale, while EPIC-CP, ICIQ-SF, IIEF 5 questionnaires and PSA levels measured quality of life and biochemical control. Pre- and post-treatment scores were compared using a paired t-test, with MID established at > 0.5 pooled SD from the baseline. A logistic regression analysis was performed to evaluate potential associations between specific patient/tumor/treatment factors and outcome deterioration. Results: From April 2021 to April 2023 a total of 50 pts were enrolled and treated. Median follow-up was 12.2 (3-27) months. No late ≥ G2 GI or GU toxicity was registered. Late G1 urinary and rectal toxicities occurred in 46 % and 4 % of patients, respectively. Among 47 patients completing all EPIC-CP domains, four (9 %) showed worsened QoL, and eleven (26 %) developed erectile dysfunction correlating with PTV D2% (P = 0.032). At Multivariate analysis bladder wall D10cc independently correlated with late G1 GU toxicity (P = 0.034). Median post-treatment PSA nadir was 0.04 ng/mL (0.00 - 0.84). At the last follow-up, six patients presented with biochemical failure, including two nodal relapses. Conclusions: Our findings show that post-prostatectomy SBRT did not result in increased toxicity nor a significant decline in QoL measures, thus showing that it can be safely extended to the postoperative setting. Long-term follow-up and randomized comparisons with different RT schedules are needed to validate this approach.

Short-term pain control after palliative radiotherapy for uncomplicated bone metastases: a prospective cohort study.

This study aimed at evaluating the efficacy of different radiotherapy (RT) fractionation regimens in managing uncomplicated painful bone metastases (BM) and identifying predictive factors for pain control. Patients with 1 to 4 symptomatic BM from any primary solid tumors and a life expectancy exceeding 3 months were included in the study and received palliative RT, with SBRT restricted in the context of oligometastatic disease or in patients with good prognosis. Pain analysis using the Brief Pain Inventory (BPI) tool was conducted at baseline, 1 and 3 months after RT. Analgesic intake was recorded as morphine-equivalent doses (OME). Pain response was assessed using the International Consensus on Palliative Radiotherapy Endpoint (ICPRE). Multivariate logistic regression analyzed patient-related, tumor-related, and treatment-related factors predicting BM pain control at 3 months post-RT. From Feb 2022 to Feb 2023, 44 patients with 65 symptomatic BM were investigated. Breast (32%) and lung (24%) tumors were the most common primary tumors. Treatment plans included 3DCRT (60%) and VMAT (40%), with a median biological effective dose for tumors (BED) of 29 Gy [14-108]. All patients completed the 3-month follow-up. Pain response rates were 62% at 1 month and 60% at 3 months. Responders had better PS ECOG scores (67%; P = 0.008) and received active systemic therapies (67%: P = 0.036). Non-responders had lower pretreatment BPI (mean: 13.7 vs. 58.2; P = 0.032), with significantly higher values after 1 month (mean: 9.1 vs. 5.3, P = 0.033). Baseline BPI (OR: 1.17; 95% CI: 1.032-1.327; P = 0.014) and BPI at 1 month (OR: 0.83; 95% CI: 0.698-0.976; P = 0.025) were independent predictors of pain response at 3 months. Our findings show that palliative RT ensured short-term pain control in patients with BM, regardless of tumor type and dose-fractionation regimen. A larger sample size and a longer follow-up could potentially identify which patients are likely to benefit most from RT, and which fractionation might be indicated for achieving a durable pain relief. A multidisciplinary approach is paramount to provide a better care to BM patients.

The Contribution of Mediastinal Transbronchial Nodal Cryobiopsy to Morpho-Histological and Molecular Diagnosis.

(1) Background: endobronchial ultrasound-guided mediastinal transbronchial cryo-node biopsy, previously assisted by fine-needle aspiration, is a novel technique of particular interest in the field of lung cancer diagnosis and is of great utility for extrathoracic tumor metastases, lymphomas, and granulomatous diseases. An integrated histological and molecular diagnosis of small samples implies additional difficulty for the pathologist. Additionally, emerging tumor biomarkers create the need to search for new approaches to better manage the tissue sample; (2) Methods: An analytical observational study of 32 mediastinal node cryobiopsies is carried out in 27 patients (n = 27). Statistical analysis using the t-student and Wilcoxon signed-rank tests for paired data is performed with SPSS 26 and R Statistical software. The significance level is established at p < 0.05; (3) Results: cryobiopsies were valid for diagnosis in 25 of 27 patients, with a maximum average size of 3.5 ± 0.7 mm. A total of 18 samples (66.67%) were positive for malignancy and 9 (33.33%) were benign. The tumor percentage measured in all neoplastic samples was greater than 30%. The average DNA and RNA extracted in nine non-small cell lung cancer cases was 97.2 ± 22.4 ng/µL and 26.6 ± 4.9 ng/µL, respectively; (4) Conclusions: the sample size obtained from an endobronchial ultrasound-guided mediastinal transbronchial cryo-node biopsy facilitates the morphological and histo-architectural assessment of inflammatory and neoplastic pathology. It optimizes molecular tests in the latter due to more tumor cells, DNA, and RNA.

Vaccination trends in people with HIV infection participanting in the hospital-based survey of patients infected with HIV, 2006-2021.

OBJECTIVE: To assess the trend in hepatitis A, hepatitis B, pneumococcal, tetanus and seasonal influenza vaccination in people with HIV infection and to analyse associated factors. METHODS: The Hospital Survey of Patients with HIV, an annual cross-sectional study conducted on a fixed day (2006-2021), was used. Inpatients and outpatients were included. Trends in vaccination and associated factors were analysed using logistic regression. RESULTS: A total of 8643 participants were included. Vaccination rates increased to 65.3% for hepatitis A, 83.7% for hepatitis B, 49.3% for tetanus, 68.9% for pneumococcal and 74.5% for seasonal influenza in 2021. Factors positively associated with vaccination were older age for pneumococcal and influenza vaccination; higher educational level for hepatitis A and tetanus; living in a closed institutions or prison for tetanus, pneumococcal and influenza; and having acquired HIV through sex between men for hepatitis A, B and pneumococcal. In addition, being on antiretroviral treatment and having a high CD4 count were positively associated with vaccination for all these diseases. Factors inversely associated with vaccination were being older (hepatitis A, B and tetanus), being an immigrant (tetanus and seasonal influenza) and being an injection drug user/ex-user for hepatitis A and B. CONCLUSIONS: Vaccination in people with HIV has increased in the study period. The results are in line with the recommendations in this population, although there is still room to reach the established vaccination indicators.

Submucosal infiltrate of anisakis larvae. Rare cause of intestinal obstruction.

Patient aged 71 with a history of type 2 diabetes mellitus. He came to the emergency department for abdominal pain and vomiting. Laboratory tests showed an increase in acute phase reactants. Abdominal CT scan showed dilated jejunal loops, compatible with intestinal occlusion. Urgent intervention was performed, resecting the affected segment. The pathology report showed a prominent transmural inflammatory infiltrate and interstitial oedema, with moderate villous atrophy, identifying parasitic structures compatible with anisakis larvae (family Anisakidae). Given the mechanism of tissue invasion, the larvae are surrounded by a predominantly eosinophilic inflammatory infiltrate, organised as granulomas or abscesses.

A case report of hepatic angiomyolipoma, inflammatory subtype. Clinico-pathological characterization: a diagnostic challenge.

BACKGROUND: Angiomyolipoma is a benign mesenchymal neoplasm of a wide histological heterogeneity belonging to the PEComa "family." The liver, after the kidney, is their second most frequent location. However, inflammatory hepatic AMLs constitute a rare entity, with only fourteen documented cases until 2020. These neoplasms can overlap morphological features of IgG4-related diseases, being of great diagnostic relevance to demonstrating myomelanocytic-lineage differentiation of the neoplastic cells. CASE PRESENTATION: we present a new case of an inflammatory hepatic AML resembling an IgG4-related disease in a 35-year-old woman with a subcapsular 5 cm mass confined to segment VII of the right hepatic lobe. Although having reduced its size along the tumor's natural evolution, complete tumor resection was decided due to its hypermetabolic behavior (max. SUV = 12,6) assessed by PET-CT scan. Finally, the patient underwent a right hepatectomy due to spontaneous rupture and bleeding of the lesion during the intervention. All the diagnostic and therapeutic procedures occurred in the last months of the COVID-19 pandemic. CONCLUSIONS: This review aims to describe inflammatory hepatic AML histological and immunohistochemical features. We further sought to establish a clinicopathological contextualization of this tumoral subtype.

Expectations of Personal Life Development and Decision-Making in People with Moderate Intellectual Disabilities.

People with intellectual disabilities have a need for personal and social development that is often unknown or poorly understood. The main motivation is the fact that students belong to a group usually excluded from the ordinary educational process. That process is replaced with measures that focus on caring for students rather than promoting their development. The objective of this research is to understand the expectations for personal development and decision-making of students with intellectual disabilities. To achieve the stated objective, a qualitative research based on two complementary approaches, grounded theory and case study, has been employed. The sample (n = 28) was drawn from a specific study program for the training and development of people with intellectual disabilities at the University of Murcia, called "We are all Campus". We aim to identify the different perceptions of their reality and potential for personal development, to understand their decision-making and what motivates them. Likewise, we investigate the self-perceptions of students with intellectual disabilities have and their understanding of their future life expectations. The main conclusions show that the training program represents an opportunity for students' progression and personal development. Thus far, the expectations of the students have remained the same, focusing on their work and social inclusion.

Immunodominant T cell peptides from four candidate malarial antigens as biomarkers of protective immunity against malaria.

A malaria vaccine with high efficacy and capable of inducing sterile immunity against malaria within genetically diverse populations is urgently needed to complement ongoing disease control and elimination efforts. Parasite-specific IFN-γ and granzyme B-secreting CD8 + T cells have been identified as key mediators of protection and the rapid identification of malaria antigen targets that elicit these responses will fast-track the development of simpler, cost-effective interventions. This study extends our previous work which used peripheral blood mononuclear cells (PBMCs) from adults with life-long exposure to malaria parasites to identify immunodominant antigen-specific peptide pools composed of overlapping 15mer sequences spanning full length proteins of four malarial antigens. Our current study aimed to identify CD8 + T cell epitopes within these previously identified positive peptide pools. Cryopreserved PBMCs from 109 HLA-typed subjects were stimulated with predicted 9-11mer CD8 + T cell epitopes from P. falciparum circumsporozoite protein (CSP), apical membrane antigen 1 (AMA1), thrombospondin related anonymous protein (TRAP) and cell traversal for ookinetes and sporozoites (CelTOS) in FluoroSpot assays. A total of 135 epitopes out of 297 tested peptides from the four antigens were experimentally identified as positive for IFN-γ and/or granzyme B production in 65 of the 109 subjects. Forty-three of 135 epitopes (32 %) were promiscuous for HLA binding, with 31 of these promiscuous epitopes (72 %) being presented by HLA alleles that fall within at least two different HLA supertypes. Furthermore, about 52 % of identified epitopes were conserved when the respective sequences were aligned with those from 16 highly diverse P. falciparum parasite strains. In summary, we have identified a number of conserved epitopes, immune responses to which could be effective against multiple P. falciparum parasite strains in genetically diverse populations.

Herpes simplex virus type 1 (HSV-1) over-infection in patients with acute respiratory distress syndrome secondary to COVID-19 pneumonia: Impact on mortality.

Objective: Herpes simplex virus type 1 (HSV-1) reactivation have been described in patients with invasive mechanical ventilation and recently in patients with acute respiratory distress syndrome (ARDS) secondary to COVID-19 with higher rates of reactivation than were detected previously in critical care, and although the diagnosis of HSV-1 pneumonia is not easy, its presence is associate with an increase in morbidity and mortality. The objective of this study is to determinate if the identification of HSV-1 in lower airway of patients with ARDS secondary to COVID-19 have influence in clinical outcome and mortality. Method: Two hundred twenty-four admitted patients in intensive care unit (ICU) of Complejo Hospitalario Universitario de Toledo diagnosed of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were reviewed and were selected those with mechanical ventilation who had undergone (BAL). It was registered all results of HSV-1 PCR (negative and positive). Results: During the study period (November 28, 2020 to April 13, 2021) was admitted 224 patients in ICU diagnosed of SARS-CoV-2 pneumonia. Eighty-three patients of them had undergone BAL, with HSV-1 PCR positive result in 47 (56%), and negative result in 36 (43.4%). We performed pathological anatomy study in BAL samples on 26 of the total BAL realized. Typical cytopathic characteristics of HSV-1 were found in 13 samples (50%) and 11 of them (84.6%) have had HSV-1 PCR positive result. Thirty days mortality was significantly higher in the group of patients with HSV-1 PCR positive result (33.5% vs. 57.4%, p = 0.015). This difference was stronger in the group of patients with HSV-1 findings in the pathological anatomy study (30.8% vs. 69.2%, p = 0.047). Conclusion: Our results suggest that ARDS secondary to SARS-CoV-2 pneumonia is highly associated to HSV-1 reactivation and that the finding of HSV-1 in lower airway is associated with a worst prognostic and with significantly mortality increase. It is necessary to carry out more extensive studies to determinate if treatment with acyclovir can improve the prognosis of these patients.

Objetivo: Las reactivaciones del virus herpes simple (VHS) están descritas en los pacientes en ventilación mecánica invasiva y recientemente en el síndrome de distrés respiratorio agudo (SDRA) por COVID-19, con tasas más altas que las descritas previamente en pacientes críticos, y aunque el diagnóstico de neumonía por VHS es difícil, su presencia se asocia con aumento de la morbimortalidad. El objetivo de este estudio es determinar si la identificación de VHS en el tracto respiratorio inferior en pacientes en ventilación mecánica con SDRA por COVID-19 influye sobre la evolución clínica y la mortalidad. Método: Se revisaron 224 pacientes ingresados en el servicio de medicina intensiva del Complejo Hospitalario de Toledo con el diagnóstico de neumonía por SARS-CoV-2 y se seleccionaron los pacientes en ventilación mecánica a los que se les había realizado lavado broncoalveolar (LBA). Se registraron todos los resultados de la PCR, tanto si fue positiva como si fue negativa para VHS. Resultados: Durante el periodo de estudio (del 28 de noviembre de 2020 hasta el 13 de abril de 2021) ingresaron 224 pacientes en la UCI con el diagnóstico de neumonía por SARS-CoV-2. De ellos, en 83 se realizó lavado broncoalveolar (LBA), siendo la PCR para VHS-1 positiva en 47 y negativa en 36 (56,6%). Realizamos estudio anatomopatológico en muestras de LBA a 26 pacientes del total de la muestra. Se encontraron características citopáticas típicas de infección por herpes en 13 (50%), de los cuales 11 (84,6%) tenían PCR positiva. La mortalidad a los 30 días fue significativamente mayor en el grupo de pacientes con PCR positiva (33,5% vs 57,4%, p = 0,015). Esta diferencia fue aún más marcada en el grupo con hallazgos anatomopatológicos compatibles con neumonía por VHS (30,8% versus 69,2%, p = 0,047). Conclusión: Nuestros resultados sugieren que el SDRA secundario a neumonía por SARS-CoV-2 se asocia a una alta reactivación del VHS y que su hallazgo en el tracto respiratorio inferior se asocia con un peor pronóstico y un aumento significativo de la mortalidad. Son necesarios estudios más amplios para determinar si el tratamiento con aciclovir puede mejorar el pronóstico de estos pacientes.

Sobreinfección respiratoria por virus herpes simple tipo1 en pacientes con SDRA secundario a neumonía grave por COVID-19. Impacto sobre la mortalidad / Herpes simplex virus type 1 (HSV-1) over-infection in patients with acute respiratory distress syndrome secondary to COVID-19 pneumonia: Impact on mortality

Objetivo: Las reactivaciones del virus herpes simple (VHS) están descritas en los pacientes en ventilación mecánica invasiva y recientemente en el síndrome de distrés respiratorio agudo (SDRA) por COVID-19, con tasas más altas que las descritas previamente en pacientes críticos, y aunque el diagnóstico de neumonía por VHS es difícil, su presencia se asocia con aumento de la morbimortalidad. El objetivo de este estudio es determinar si la identificación de VHS en el tracto respiratorio inferior en pacientes en ventilación mecánica con SDRA por COVID-19 influye sobre la evolución clínica y la mortalidad.MétodoSe revisaron 224 pacientes ingresados en el servicio de medicina intensiva del Complejo Hospitalario de Toledo con el diagnóstico de neumonía por SARS-CoV-2 y se seleccionaron los pacientes en ventilación mecánica a los que se les había realizado lavado broncoalveolar (LBA). Se registraron todos los resultados de la PCR, tanto si fue positiva como si fue negativa para VHS.ResultadosDurante el periodo de estudio (del 28 de noviembre de 2020 hasta el 13 de abril de 2021) ingresaron 224 pacientes en la UCI con el diagnóstico de neumonía por SARS-CoV-2. De ellos, en 83 se realizó lavado broncoalveolar (LBA), siendo la PCR para VHS-1 positiva en 47 y negativa en 36 (56,6%). Realizamos estudio anatomopatológico en muestras de LBA a 26 pacientes del total de la muestra. Se encontraron características citopáticas típicas de infección por herpes en 13 (50%), de los cuales 11 (84,6%) tenían PCR positiva. La mortalidad a los 30días fue significativamente mayor en el grupo de pacientes con PCR positiva (33,5% vs 57,4%, p=0,015). Esta diferencia fue aún más marcada en el grupo con hallazgos anatomopatológicos compatibles con neumonía por VHS (30,8% versus 69,2%, p=0,047). (AU)

Objective: Herpes simplex virus type1 (HSV-1) reactivation have been described in patients with invasive mechanical ventilation and recently in patients with acute respiratory distress syndrome (ARDS) secondary to COVID-19 with higher rates of reactivation than were detected previously in critical care, and although the diagnosis of HSV-1 pneumonia is not easy, its presence is associate with an increase in morbidity and mortality. The objective of this study is to determinate if the identification of HSV-1 in lower airway of patients with ARDS secondary to COVID-19 have influence in clinical outcome and mortality.MethodTwo hundred twenty-four admitted patients in intensive care unit (ICU) of Complejo Hospitalario Universitario de Toledo diagnosed of severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) were reviewed and were selected those with mechanical ventilation who had undergone (BAL). It was registered all results of HSV-1 PCR (negative and positive).ResultsDuring the study period (November 28, 2020 to April 13, 2021) was admitted 224 patients in ICU diagnosed of SARS-CoV-2 pneumonia. Eighty-three patients of them had undergone BAL, with HSV-1 PCR positive result in 47 (56%), and negative result in 36 (43.4%). We performed pathological anatomy study in BAL samples on 26 of the total BAL realized. Typical cytopathic characteristics of HSV-1 were found in 13 samples (50%) and 11 of them (84.6%) have had HSV-1 PCR positive result. Thirty days mortality was significantly higher in the group of patients with HSV-1 PCR positive result (33.5% vs. 57.4%, P=.015). This difference was stronger in the group of patients with HSV-1 findings in the pathological anatomy study (30.8% vs. 69.2%, P=.047). (AU)

[Herpes simplex virus type 1 (HSV-1) over-infection in patients with acute respiratory distress syndrome secondary to COVID-19 pneumonia: Impact on mortality]. / Sobreinfección respiratoria por virus herpes simple tipo1 en pacientes con SDRA secundario a neumonía grave por COVID-19. Impacto sobre la mortalidad.

OBJECTIVE: Herpes simplex virus type1 (HSV-1) reactivation have been described in patients with invasive mechanical ventilation and recently in patients with acute respiratory distress syndrome (ARDS) secondary to COVID-19 with higher rates of reactivation than were detected previously in critical care, and although the diagnosis of HSV-1 pneumonia is not easy, its presence is associate with an increase in morbidity and mortality. The objective of this study is to determinate if the identification of HSV-1 in lower airway of patients with ARDS secondary to COVID-19 have influence in clinical outcome and mortality. METHOD: Two hundred twenty-four admitted patients in intensive care unit (ICU) of Complejo Hospitalario Universitario de Toledo diagnosed of severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) were reviewed and were selected those with mechanical ventilation who had undergone (BAL). It was registered all results of HSV-1 PCR (negative and positive). RESULTS: During the study period (November 28, 2020 to April 13, 2021) was admitted 224 patients in ICU diagnosed of SARS-CoV-2 pneumonia. Eighty-three patients of them had undergone BAL, with HSV-1 PCR positive result in 47 (56%), and negative result in 36 (43.4%). We performed pathological anatomy study in BAL samples on 26 of the total BAL realized. Typical cytopathic characteristics of HSV-1 were found in 13 samples (50%) and 11 of them (84.6%) have had HSV-1 PCR positive result. Thirty days mortality was significantly higher in the group of patients with HSV-1 PCR positive result (33.5% vs. 57.4%, P=.015). This difference was stronger in the group of patients with HSV-1 findings in the pathological anatomy study (30.8% vs. 69.2%, P=.047). CONCLUSION: Our results suggest that ARDS secondary to SARS-CoV-2 pneumonia is highly associated to HSV-1 reactivation and that the finding of HSV-1 in lower airway is associated with a worst prognostic and with significantly mortality increase. It is necessary to carry out more extensive studies to determinate if treatment with acyclovir can improve the prognosis of these patients.

In vitro production of infectious Plasmodium falciparum sporozoites.

An effective vaccine is needed for the prevention and elimination of malaria. The only immunogens that have been shown to have a protective efficacy of more than 90% against human malaria are Plasmodium falciparum (Pf) sporozoites (PfSPZ) manufactured in mosquitoes (mPfSPZ)1-7. The ability to produce PfSPZ in vitro (iPfSPZ) without mosquitoes would substantially enhance the production of PfSPZ vaccines and mosquito-stage malaria research, but this ability is lacking. Here we report the production of hundreds of millions of iPfSPZ. iPfSPZ invaded human hepatocytes in culture and developed to mature liver-stage schizonts expressing P. falciparum merozoite surface protein 1 (PfMSP1) in numbers comparable to mPfSPZ. When injected into FRGhuHep mice containing humanized livers, iPfSPZ invaded the human hepatocytes and developed to PfMSP1-expressing late liver stage parasites at 45% the quantity of cryopreserved mPfSPZ. Human blood from FRGhuHep mice infected with iPfSPZ produced asexual and sexual erythrocytic-stage parasites in culture, and gametocytes developed to PfSPZ when fed to mosquitoes, completing the P. falciparum life cycle from infectious gametocyte to infectious gametocyte without mosquitoes or primates.

Cellular interferon-gamma and interleukin-2 responses to SARS-CoV-2 structural proteins are broader and higher in those vaccinated after SARS-CoV-2 infection compared to vaccinees without prior SARS-CoV-2 infection.

Class I- and Class II-restricted epitopes have been identified across the SARS-CoV-2 structural proteome. Vaccine-induced and post-infection SARS-CoV-2 T-cell responses are associated with COVID-19 recovery and protection, but the precise role of T-cell responses remains unclear, and how post-infection vaccination ('hybrid immunity') further augments this immunity To accomplish these goals, we studied healthy adult healthcare workers who were (a) uninfected and unvaccinated (n = 12), (b) uninfected and vaccinated with Pfizer-BioNTech BNT162b2 vaccine (2 doses n = 177, one dose n = 1) or Moderna mRNA-1273 vaccine (one dose, n = 1), and (c) previously infected with SARS-CoV-2 and vaccinated (BNT162b2, two doses, n = 6, one dose n = 1; mRNA-1273 two doses, n = 1). Infection status was determined by repeated PCR testing of participants. We used FluoroSpot Interferon-gamma (IFN-γ) and Interleukin-2 (IL-2) assays, using subpools of 15-mer peptides covering the S (10 subpools), N (4 subpools) and M (2 subpools) proteins. Responses were expressed as frequencies (percent positive responders) and magnitudes (spot forming cells/106 cytokine-producing peripheral blood mononuclear cells [PBMCs]). Almost all vaccinated participants with no prior infection exhibited IFN-γ, IL-2 and IFN-γ+IL2 responses to S glycoprotein subpools (89%, 93% and 27%, respectively) mainly directed to the S2 subunit and were more robust than responses to the N or M subpools. However, in previously infected and vaccinated participants IFN-γ, IL-2 and IFN-γ+IL2 responses to S subpools (100%, 100%, 88%) were substantially higher than vaccinated participants with no prior infection and were broader and directed against nine of the 10 S glycoprotein subpools spanning the S1 and S2 subunits, and all the N and M subpools. 50% of uninfected and unvaccinated individuals had IFN-γ but not IL2 or IFN-γ+IL2 responses against one S and one M subpools that were not increased after vaccination of uninfected or SARS-CoV-2-infected participants. Summed IFN-γ, IL-2, and IFN-γ+IL2 responses to S correlated with IgG responses to the S glycoprotein. These studies demonstrated that vaccinations with BNT162b2 or mRNA-1273 results in T cell-specific responses primarily against epitopes in the S2 subunit of the S glycoprotein, and that individuals that are vaccinated after SARS-CoV-2 infection develop broader and greater T cell responses to S1 and S2 subunits as well as the N and M proteins.

Ocio familiar en tiempos de confinamiento: construcción y validación de un instrumento / Family leisure during lockdowns: Construction and validation of an instrument / Lazer em família em tempos de confinamento: Construção e validação de um instrumento

Resumen (analítico) La revalorización experimentada por el ocio en los contextos familiares, debido a las restricciones sociales que han conllevado un incremento del tiempo en casa, ha contribuido a que esta emerja con fuerza como línea de investigación educativa, pues hasta ahora se encontraba desatendida en el panorama español. En el presente estudio se diseña y valida el Cuestionario sobre ocio familiar durante el confinamiento. Para dotar de validez de contenido y consistencia al constructo, se contó con el juicio de 10 expertos sobre la claridad, pertinencia y adecuación del instrumento, mediante una escala de validación. Los resultados denotan que el cuestionario resultante (61 ítems) posee propiedades psicométricas adecuadas que lo convierten en una herramienta apropiada para evaluar el ocio familiar, quedando confirmado su rigor y valía como correcto instrumento de análisis.

Abstract (analytical) The revaluation of leisure in family contexts, caused by lockdowns imposed during the COVID-19 pandemic that led to an increase in time spent at home, has contributed to this area emerging as a focus of educational research, which until now had been neglected in Spanish-speaking countries. In the present study, the authors present the process of designing and validating a "Questionnaire on family leisure during lockdowns". In order to provide content validity and consistency to the design of the instrument, feedback from 10 experts assessed the clarity, relevance and suitability of the instrument using a validation scale. The results show that the questionnaire, with 61 questions, has sufficient psychometric properties that make it an appropriate tool to evaluate family leisure. During this process the authors confirmed its rigor and value as an analytical instrument for research.

Resumo (analítico) A revalorização vivenciada pelo lazer em contextos familiares, devido às restrições sociais que têm levado ao aumento do tempo em casa, tem contribuído para o seu surgimento fortemente como uma linha de pesquisa educacional, já que até então era negligenciada no cenário espanhol. No presente estudo, o "Questionário sobre lazer familiar durante o confinamento" é elaborado e validado. Para conferir validade de conteúdo e consistência ao construto, o julgamento de 10 especialistas contou com a clareza, pertinência e adequação do instrumento, por meio de uma escala de validação. Os resultados mostram que o questionário resultante (61 itens) possui propriedades psicométricas adequadas que o tornam um instrumento adequado para avaliar o lazer familiar, confirmando seu rigor e valor como um correto instrumento de análise.

La implementación de Twitter e Instagram como herramientas complementarias durante las prácticas presenciales de histología / The implementation of Twitter and Instagram as complementary tools during face-to-face practical lessons of Histology

Introducción: La pandemia de la COVID-19 ha multiplicado el uso de redes sociales en la enseñanza médica, tanto de pregrado como de posgrado, debido a las restricciones sanitarias impuestas. Nuestro objetivo fue implementar el uso de Twitter e Instagram en las prácticas de histología para superar dichas limitaciones.Material y métodos.Se describe la utilización de Twitter e Instagram para el estudio práctico de histología tanto dentro como fuera del aula. Tras la finalización de las prácticas, los alumnos cumplimentaron una encuesta de satisfacción vía Google Form, cuyos resultados se sometieron posteriormente a análisis estadístico.Resultados.La encuesta fue completada por 261 alumnos. Un 86,6% pensó que el uso de estas redes sociales mejoró la dinámica global de la práctica. Asimismo, los alumnos percibieron que, gracias a estas herramientas, su nivel de implicación (70,9%) y atención (59,5%) aumentó durante las practicas. Finalmente, un 63,1% consideró muy útiles para su estudio las publicaciones subidas por el profesorado a Instagram.Conclusión.Twitter e Instagram constituyen recursos muy útiles para la enseñanza práctica en histología, ya que los alumnos se muestran bastante satisfechos y motivados con el uso de estas redes sociales para su aprendizaje. (AU)

Introduction: COVID-19 pandemic has doubled the use of Social Networks in medical education, both at undergraduate and postgraduate level, due to the sanitary restrictions affecting social distance. For that reason, we decided to implement the use of Twitter and Instagram during histological practical lessons in order to overcome these limitations.Material and methods.Use of Twitter and Instagram for practical learning in Histology both inside and outside the classroom. After the practical lessons, students filled a satisfaction survey via Google Forms, whose results were then analyzed statistically.Results.The survey was filled by 261 students. 86,6% of them thought that the use of social networks improved the global dynamics of the practical lessons. In the same way, most of the students perceived that thanks to these tools their implication (70,9%) and attention (59,5%) increased during the practices. Finally, 63,1% considered very useful for their study the Instagram posts uploaded by professors.Conclusion.Twitter and Instagram arise as useful resources for practical education in Histology since students appear to be satisfied and motivated with the use of these social networks for their learning. (AU)

Radiochemotheraphy-induced oral mucositis: Ectoin solution as a new treatment.

Background: The current treatment for head and neck cancer involves radiotherapy, systemic therapy and surgery in a multidisciplinary approach. Unfortunately, cancer therapies can lead to local and systemic complications or side effects such as mucositis, which is the most common dose-dependent complication in the oral cavity and gastrointestinal tract. Mucositis can cause a considerably reduced quality of life in cancer patients already suffering from physical and psychological exhaustion. Moreover, radiotherapy interruptions due to toxicity can impact negatively in local control and survival. The main purpose of this study was to analyze patient satisfaction of Ectoin solution use in radiotherapy or radiochemotherapy-induced oral mucositis. Material and Methods: This is an institutional prospective analysis including 15 patients, conducted by two Spanish centers, between October 2019 and May 2020. Patients were treated with Ectoin solution during Radiotherapy and one month after the end of the treatment, three times per day. A seven-ítem Likert scale was used. We present our descriptive statistic regarding doctors and patients´s satisfaction. Results: Our results suggest that Ectoin solution relieves mucositis and is well tolerated by patients. Conclusions: We observed a favorable repercussion in the oral mucositis management and suggest a potential benefit of treating it. Key words:Radiotherapy, oral mucositis, head and neck cancer, ectoine, oral care.

CHARM: COVID-19 Health Action Response for Marines-Association of antigen-specific interferon-gamma and IL2 responses with asymptomatic and symptomatic infections after a positive qPCR SARS-CoV-2 test.

SARS-CoV-2 T cell responses are associated with COVID-19 recovery, and Class I- and Class II-restricted epitopes have been identified in the spike (S), nucleocapsid (N) and membrane (M) proteins and others. This prospective COVID-19 Health Action Response for Marines (CHARM) study enabled assessment of T cell responses against S, N and M proteins in symptomatic and asymptomatic SARS-CoV-2 infected participants. At enrollment all participants were negative by qPCR; follow-up occurred biweekly and bimonthly for the next 6 weeks. Study participants who tested positive by qPCR SARS-CoV-2 test were enrolled in an immune response sub-study. FluoroSpot interferon-gamma (IFN-γ) and IL2 responses following qPCR-confirmed infection at enrollment (day 0), day 7 and 14 and more than 28 days later were measured using pools of 17mer peptides covering S, N, and M proteins, or CD4+CD8 peptide pools containing predicted epitopes from multiple SARS-CoV-2 antigens. Among 124 asymptomatic and 105 symptomatic participants, SARS-CoV-2 infection generated IFN-γ responses to the S, N and M proteins that persisted longer in asymptomatic cases. IFN-γ responses were significantly (p = 0.001) more frequent to the N pool (51.4%) than the M pool (18.9%) among asymptomatic but not symptomatic subjects. Asymptomatic IFN-γ responders to the CD4+CD8 pool responded more frequently to the S pool (55.6%) and N pool (57.1%), than the M pool (7.1%), but not symptomatic participants. The frequencies of IFN-γ responses to the S and N+M pools peaked 7 days after the positive qPCR test among asymptomatic (S pool: 22.2%; N+M pool: 28.7%) and symptomatic (S pool: 15.3%; N+M pool 21.9%) participants and dropped by >28 days. Magnitudes of post-infection IFN-γ and IL2 responses to the N+M pool were significantly correlated with IFN-γ and IL2 responses to the N and M pools. These data further support the central role of Th1-biased cell mediated immunity IFN-γ and IL2 responses, particularly to the N protein, in controlling COVID-19 symptoms, and justify T cell-based COVID-19 vaccines that include the N and S proteins.

Effects of Kangaroo Mother Care in the NICU on the Physiological Stress Parameters of Premature Infants: A Meta-Analysis of RCTs.

OBJECTIVE: The aim of this study was to analyze the randomised controlled trials that explored the effect of kangaroo mother care on physiological stress parameters of premature infants. METHODS: Two independent researchers performed a systematic review of indexed studies in PubMed, Embase, CINAHL, Cochrane and Scopus. We included data from randomized controlled trials measuring the effects of kangaroo care compared to standard incubator care on physiological stress outcomes, defined as oxygen saturation, body temperature, heart rate and respiratory rate. The PRISMA model was used to conduct data extraction. We performed a narrative synthesis of all studies and a meta-analysis when data were available from multiple studies that compared the same physiological parameters with the kangaroo method as an intervention and controls and used the same outcome measures. RESULTS: Twelve studies were eligible for inclusion in this meta-analysis. According to statistical analysis, the mean respiratory rate of preterm infants receiving KMC was lower than that of infants receiving standard incubator care (MD, -3.50; 95% CI, -5.17 to -1.83; p < 0.00001). Infants who received kangaroo mother care had a higher mean heart rate, oxygen saturation and temperature, although these results were not statistically significant. CONCLUSIONS: Current evidence suggests that kangaroo care in the neonatal intensive care unit setting is a safe method that may have a significant effect on some of the physiological parameters of stress in preterm infants. However, due to clinical heterogeneity, further studies are needed to assess the effects of physiological stress in the neonatal intensive care unit on the development of preterm infants.

Role of green innovation, trade and energy to promote green economic growth: a case of South Asian Nations.

The objective of this study is to contribute to the existing debate of green economic growth by empirically investigating the role of cleaner energy production, green innovation, and green trade in green economic growth in the context of South Asian countries. For this purpose, the study collects the data of South Asian Economies for 2000-2018 from different sources such as world development indicators (WDI), International Energy Statistics (IES), and Organization for Economic Co-operation and Development (OECD) statistics. The study applied Pesaran's (2007) second-generation unit root test to test the stationarity of the data. Wasteland's (2007) test of cointegration was applied to examine the long-run association among modeled variables. The study confirmed the long-run association among modeled variables that turn to be stationary at the first differences. Moreover, the study applied fully modified least square (FMOLS) and dynamic least square (DOLS) to estimate the empirical results of the study. Results of the study show that the production of clean energy, green innovation, and green trade positively contributes to the green economic growth of South Asian Economies Graphical abstract.

Kangaroo mother care and skin-to-skin care in preterm infants in the neonatal intensive care unit: A bibliometric analysis.

BACKGROUND: The desire to understand and the growing interest in research on the effects of kangaroo mother care in preterm infants in the neonatal intensive care unit have led to a significant increase in the number of manuscripts published in this field over the past decade. It is therefore necessary to regularly review the state of knowledge on this phenomenon in order to identify progress and constraints, to stimulate reflection, and to encourage progress in future research. PURPOSE: The aim of this study was to determine the current state of scientific production in relation to kangaroo mother care in preterm infants in the neonatal intensive care unit through bibliometric analysis. DATA SOURCES: This study presents a review of 212 published papers from the Scopus database (1990-2019). DATA EXTRACTION: Two processing software applications were used: VOSviewer and SciMAT. In addition, through a keyword analysis, this study established the hot spot research trends to be developed in future work. The study adhered to the PRISMA-ScR guidelines for quality improvement studies as part of the EQUATOR network. RESULTS: Our results show that research in this field is going through a time of high productivity and we could sort this growing body of work into different periods, highlighting the most important topics.The analysis shows that most research in this field is focused on five motor topics. These are: prematurity, male, psychology, intensive care neonatal, and major clinical study. The analysis also allowed us to identify four basic and cross-disciplinary topics that need to be developed and that emerge as future research directions: preterm infants, child-parent relations, child development, and skin-to-skin contact. IMPLICATIONS FOR PRACTICE AND RESEARCH: The main contribution of this work is the creation of a knowledge map on the research in this field. This article provides information on how we can shape the future to provide optimal care for these infants and their parents.